The present invention relates generally to the preparation of 2-piperidineethanol compounds, and more specifically to improved processes for preparing 2-piperidineethanol compounds involving the hydrogenation of corresponding 2-pyridineethanol compounds in the presence of hydrogenation catalysts.
As further background, 2-(2-Hydroxyethyl)piperidine (also known as 2-piperidineethanol or 2-ethanolpiperidine) and related piperidine compounds are useful inter alia as intermediates to pharmacological agents and insect repellents. Various processes for preparing 2-piperidineethanol and related compounds have been described. For example, several references in the literature describe the preparation of 2-piperidineethanol via the catalytic hydrogenation of 2-pyridineethanol. Illustratively, T. S. Hamilton et al., J. Am. Chem. Soc., Vol. 50, pp. 2260-2263 (1928), describes the preparation of 2-piperidineethanol hydrochloride by the catalytic reduction of 2-pyridineethanol hydrochloride in ethanol at room temperature in the presence of a platinum-oxide platinum black catalyst. A number of other references describe similar or related reductions in the presence of platinum oxide catalysts in mixed solvents containing acetic acid and either water or ethanol. See, R. R. Burtner et al., J. Am. Chem. Soc., Vol. 69, pp. 630-633 (1947); E. A. Steck et al., J. Am. Chem. Soc., Vol. 81, pp. 6511-6514 (1959); and M. Rink et al., 60 Arch. Pharm., pp. 74-82 (1960).
Other catalyst and solvent combinations have also been tried. As examples, M. Freifelder et al., J. Org. Chem., Vol. 26, pp. 3805-3808 (1961), describes a hydrogenation of 2-pyridineethanol in methanol in the presence of a ruthenium dioxide catalyst to produce 2-piperidineethanol. In later-reported work, M. Freifelder et al., J. Org. Chem., Vol. 62, pp. 284-286 (1962) describe the preparation of 2-piperidineethanol by hydrogenating the corresponding pyridine in an ethanol solvent in the presence of a rhodium on carbon catalyst. E. R. Lavagnino et al., J. Am. Chem. Soc., Vol. 82, pp. 2609-2613 (1960), describes a hydrogenation of 2-pyridineethanol with a palladium on carbon catalyst in water to form the corresponding piperidine.
2-piperidineethanol has also been formed by the reductive cleavage of appropriate cyclic salts of pyridine-N-oxide, as disclosed by V. Boekelheide et al, J. Am. Chem. Soc., Vol. 80, pp. 2217-2220 (1958).
In light of the background in this area, there has remained a need and demand for effective commercial routes to 2-piperidineethanol compounds. Such routes will desirably provide high yields and selectivities, while employing readily available starting materials and minimizing the formation of undesired byproducts that may interfere with subsequent purification or use of the 2-piperidineethanol products. The embodiments of the present invention address these needs.